Skip to main content
SpringerLink
Log in

Optimized production, quality control and biodistribution assessment of 166Ho–DOTATOC: a novel radiolabelled somatostatin analog

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Nowadays, peptide receptor radionuclide therapy is used to treat a specific type of cancer called neuroendocrine tumors. In this research, the optimized conditions for 166Ho-DOTATOC production are presented. The radiolabeled compound was prepared with the specific activity of 11.1 TBq/mmol and radiochemical purity of more than 99% (using ITLC and HPLC). Stability tests of the complex were investigated in room temperature and in human serum at 37 °C. Biodistribution studies in Syrian rats showed considerable accumulation in pancreas as the somatostatin receptor-positive tissue. 166Ho-DOTATOC can be considered as a novel agent for treatment of somatostatin receptor-positive tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jamous M, Haberkorn U, Mier W (2013) Synthesis of peptide radiopharmaceuticals for the therapy and diagnosis of tumor diseases. Molecules 18:3379–3409

    Article  CAS  Google Scholar 

  2. Reubi JC, Laissue J, Krenning E, Lamberts SW (1992) Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol 43:27–35

    Article  CAS  Google Scholar 

  3. Rufini V, Calcagni ML, Baum RP (2006) Imaging of neuroendocrine tumors. Semin Nucl Med 36:228–247

    Article  Google Scholar 

  4. Stolz B, Weckbecker G, Smith-Jones PM, Albert R, Raulf F, Bruns C (1998) The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-DPhe1, Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumors. Eur J Nucl Med 25:668–674

    Article  CAS  Google Scholar 

  5. Lewis JS, Wang M, Laforest R, Wang F, Erion JL, Bugaj JE, Srinivasan A, Anderson CJ (2001) Toxicity and dosimetry of 177Lu-DOTA-Y3-octreotate in a rat model. Int J Cancer 94:873–877

    Article  CAS  Google Scholar 

  6. Modlin IM, Moss SF, Oberg K, Padbury R, Hicks RJ, Gustafsson BI, Wright NA, Kidd M (2010) Gastrointestinal neuroendocrine (carcinoid) tumors: current diagnosis and management. Med J Aust 193:46–52

    Google Scholar 

  7. Lamberts SWJ, Barker WH, Reubi JC, Krenning EP (1990) Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 323:1246–1249

    Article  CAS  Google Scholar 

  8. Maecke HR, Béhé M, Froidevaux S, Heppler A, Jermann E (1997) DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC): a unique somatostatin receptor ligand for label ing with a variety of metallic radionuclides [abstract]. J Nucl Med 38(suppl):18P

    Google Scholar 

  9. Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, Brandau W, Bockisch A, Boy C (2013) Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic euroendocrine tumors. Recent Results Cancer Res 194:353–371

    Article  CAS  Google Scholar 

  10. Forrer F, Uusijärvi H, Storch D, Maecke HR, Mueller-Brand J (2005) Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med 46:1310–1316

    CAS  Google Scholar 

  11. Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Mäcke HR, Rochlitz C, Müller-Brand J, Walter MA (2011) Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 29:2416–2423

    Article  CAS  Google Scholar 

  12. Barbieri F, Bajetto A, Pattarozzi A, Gatti M, Würth R, Thellung S, Corsaro A, Villa V, Nizzari M, Florio T (2013) Peptide receptor targeting in cancer: the somatostatin paradigm. Int J Pept 2013:926295

    Article  Google Scholar 

  13. Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QKT, Maecke HR, Müller-Brand J, Rochlitz C, Briel M, Schindler C, Walter MA (2014) Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumors. Eur J Nucl Med Mol Imaging 41:214–222

    Article  CAS  Google Scholar 

  14. O’Donoghue JA, Bardiès M, Wheldon TE (1995) Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med 36:1902–1909

    Google Scholar 

  15. Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, Ng QK, Mäcke HR, Müller-Brand J, Rochlitz C, Briel M, Walter MA (2012) Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 30:1100–1106

    Article  CAS  Google Scholar 

  16. Hubalewska-Dydejczyk A, Signore A, de Jong M, Dierckx RA, Buscombe J, Van de Wiele C (2015) Somatostatin analogues: from research to clinical practice. Wiley, Hoboken

    Book  Google Scholar 

  17. de Jong M, Breeman WA, Bernard BF, Bakker WH, Visser TJ, Kooij PP, van Gameren A, Krenning EP (2001) Tumor response after [(90)Y-DOTA(0), Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size. J Nucl Med 42:1841–1846

    Google Scholar 

  18. Calhoun JM, Cessna JT, Coursey BM, Hoppes DD, Schima FJ, Unterweger MP (1992) Standardization of holmium-166 by the CIEMAT/NIST liquid scintillation efficiency-tracing method. Radioact Radiochem 2:38–45

    Google Scholar 

  19. Zolghadri S, Jalilian AR, Naseri Z, Yousefnia H, Bahrami-Samani A, Ghannadi-Maragheh M, Afarideh H (2013) Production, quality control and biological evaluation of 166Ho-PDTMP as a possible bone palliation agent. Iran J Basic Med Sci 16:719–725

    CAS  Google Scholar 

  20. Uusijärvi H, Bernhardt P, Rösch F, Maecke HR, Forssell-Aronsson E (2006) Electron- and positron-emitting radiolanthanides for therapy: aspects of dosimetry and production. J Nucl Med 47:807–814

    Google Scholar 

  21. Kim JK, Han KH, Lee JT, Paik YH, Ahn SH, Lee JD, Lee KS, Chon CY, Moon YM (2006) Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with Holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma. Clin Cancer Res 12:543–548

    Article  CAS  Google Scholar 

  22. Rajendran JG, Eary JF, Bensinger W, Durack LD, Vernon C, Fritzberg A (2002) High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation. J Nucl Med 43:1383–1390

    CAS  Google Scholar 

  23. Yousefnia H, Amraei N, Hosntalab M, Zolghadri S, Bahrami-Samani A (2015) Preparation and biological evaluation of 166Ho-BPAMD as a potential therapeutic bone-seeking agent. J Radioanal Nucl Chem 304:1285–1291

    Article  CAS  Google Scholar 

  24. Zolghadri S, Jalilian AR, Yousefnia H, Bahrami-Samani A, Shirvani-Arani S, Ghannadi-Maragheh M (2011) Preparation and quality control of 166Ho-DTPA-antiCD20 for radioimmunotherapy. Radiochim Acta 99:237–242

    Article  CAS  Google Scholar 

  25. Nosrati S, Shanehsazzadeh S, Yousefnia H, Gholami A, Grüttner C, Jalilian AR, Hosseini RH, Lahooti A (2016) Biodistribution evaluation of 166Ho–DTPA–SPION in normal rats. J Radioanal Nucl Chem 307:1559–1566

    Article  CAS  Google Scholar 

  26. IAEA (2003) Manual for reactor produced radioisotopes. IAEA, Wien

  27. Yousefnia H, Zolghadri S, Sadeghi HR, Naderi M, Jalilian AR, Shanehsazzadeh S (2016) Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy: comparison with 177Lu-EDTMP. J Radioanal Nucl Chem 307:1243–1251

    Article  CAS  Google Scholar 

  28. Yousefnia H, Mousavi-Daramoroudi M, Zolghadri S, Abbasi-Davani F (2016) Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies. IJNM 24:85–91

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Engineering, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran

    Arsam Golabi-dezfoli & Mohammad Hosntalab

  2. Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran

    Hassan Yousefnia & Samaneh Zolghadri

Authors
  1. Arsam Golabi-dezfoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hassan Yousefnia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Hosntalab
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samaneh Zolghadri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hassan Yousefnia.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Golabi-dezfoli, A., Yousefnia, H., Hosntalab, M. et al. Optimized production, quality control and biodistribution assessment of 166Ho–DOTATOC: a novel radiolabelled somatostatin analog. J Radioanal Nucl Chem 312, 329–335 (2017). https://doi.org/10.1007/s10967-017-5225-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-017-5225-y

Keywords

Search

Navigation